Safety of Short-Term Treatments with Oral Chloroquine and Hydroxychloroquine in Patients with and without COVID-19: A Systematic Review.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have recently become the focus of global attention as possible treatments for Coronavirus Disease 2019 (COVID-19). The current systematic review aims to assess their safety in short treatments (≤14 days), whether used alone or in combination with other drugs. Following the PRISMA and SWiM recommendations, a search was conducted using four health databases for all relevant English-, Chinese-, and Spanish-language studies from inception through 30 July 2021. Patients treated for any condition and with any comparator were included. The outcomes of interest were early drug adverse effects and their frequency. A total of 254 articles met the inclusion criteria, including case and case-control reports as well as cross-sectional, cohort, and randomised studies. The results were summarised either qualitatively in table or narrative form or, when possible (99 studies), quantitatively in terms of adverse event frequencies. Quality evaluation was conducted using the CARE, STROBE, and JADAD tools. This systematic review showed that safety depended on drug indication. In COVID-19 patients, cardiac adverse effects, such as corrected QT interval prolongation, were relatively frequent (0-27.3% and up to 33% if combined with azithromycin), though the risk of torsade de pointes was low. Compared to non-COVID-19 patients, COVID-19 patients experienced a higher frequency of cardiac adverse effects regardless of the regimen used. Dermatological adverse effects affected 0-10% of patients with autoimmune diseases and COVID-19. A broad spectrum of neuropsychiatric adverse effects affected patients treated with CQ for malaria with variable frequencies and some cases were reported in COVID-19 patients. Gastrointestinal adverse effects occurred regardless of drug indication affecting 0-50% of patients. In conclusion, CQ and HCQ are two safe drugs widely used in the treatment of malaria and autoimmune diseases. However, recent findings on their cardiac and neuropsychiatric adverse effects should be considered if these drugs were to be proposed as antivirals again.

Integración de la farmacovigilancia en la rutina del servicio de farmacia: nueve años de experiencia / Integrating pharmacovigilance into the routine of pharmacy department: experience of nine years

Objetivo: Describir un programa de farmacovigilancia llevado a cabo por un servicio de farmacia y analizar las sospechas de reacciones adversas a medicamentos recogidas. Método: Estudio observacional, longitudinal, de nueve años de duración (2008-2016). El programa de farmacovigilancia está liderado por el servicio de farmacia, que realiza farmacovigilancia prospectiva, retrospectiva, intensiva y voluntaria en el paciente hospitalizado y ambulatorio (urgencias, hospital de día, consultas externas y centros sociosanitarios). Las reacciones adversas se incorporan en la historia clínica electrónica del paciente y se añade una alerta que indica su presencia. Resultados: Se recogieron 2.631 reacciones adversas a medicamentos en 2.436 pacientes (52% varones) con una media [rango] de edad de 63,3 [0-98] años. El 92,8% de las reacciones fueron notificadas por el farmacéutico y el 7,2% por médicos, enfermería y técnicos. El 63,7% se notificaron en hospitalización, el 19,2% en urgencias, el 10,6% en consultas externas, el 6,2% en hospital de día y el 0,3% en radiología. Se observó un incremento de notificación por farmacovigilancia prospectiva e intensiva. Los grupos terapéuticos mayoritariamente implicados fueron: antineoplásicos (21,3%), antibacterianos (12,3%), antitrombóticos (7,7%), analgésicos (6,7%), corticosteroides (5,2%), psicolépticos (5,2%), diuréticos (4,9%), antivirales (4,9%), antiinflamatorios y antirreumáticos (4,2%) e inmunosupresores (3,3%). Las reacciones adversas detectadas afectaron mayoritariamente a la piel y anejos (19,7%) y al tracto gastrointestinal (19,1%). Respecto a su gravedad, el 38,7% fueron leves, el 30,8% graves y el 30,5% moderadas. El 60,9% de los pacientes se recuperaron de las reacciones adversas y el 31,7% se encontraban en proceso de recuperación. Se interrumpió el tratamiento en el 65% de los casos y el 56% de los pacientes recibieron tratamiento específico. Conclusiones: La incorporación del programa de farmacovigilancia en la rutina diaria del farmacéutico de hospital aporta un valor añadido a la seguridad de la farmacoterapia del paciente

Objective: To describe our pharmacovigilance program and to analyze the reported adverse drug reactions. Method: Observational longitudinal study conducted from 2008 to 2016. The Pharmacy Department leads the pharmacovigilance program and performs prospective, retrospective, intensive, and spontaneous reporting of inpatients and outpatients (emergencies, day hospital, external consultations, and nursing homes). Each adverse drug reaction is incorporated in the electronic health record of the patient along with an alert. Results: A total of 2,631 adverse drug reactions were reported in 2,436 patients. Of these patients, 52% were men with a mean age of 63.3 [0-98] years. A total of 92.8% drug events were reported by the pharmacists and 7.2% by doctors, nurses, and technicians. A total of 63.7% were reported in inpatients, 19.2% in emergencies, 10.6% in external consultations, 6.2% in the day hospital, and 0.3% in diagnostic radiology. There was an increase in adverse drug reactions detected by prospective and intensive pharmacovigilance. Principal therapeutic groups involved in adverse drug events were antineoplastic agents (21.3%), antibacterials (12.3%), antithrombotics (7.7%), analgesics (6.7%), corticosteroids (5.2%), psycholeptics (5.2%), diuretics (4.9%), anti virals (4.9%), antiinflammatories and antirheumatics (4.2%), and immunosupressants (3.3%). Adverse drug reactions mainly affected the skin and appendages (19.7%) and gastrointestinal tract (19.1%). Adverse drug reactions were mild (38.7%), severe (30.8%), and moderate (30.5%). In total, 60.9% of patients recovered from drug events and 31.7% were in recovery. The most frequent response was treatment interruption in 65% of cases and the patients received additional specific treatment in 56% of cases. Conclusions: The incorporation of the pharmacovigilance program within the daily routine of the hospital pharmacist provides added value to the safety and pharmacotherapy of the patient

Integrating pharmacovigilance into the routine of pharmacy department: experience of nine years.

OBJECTIVE: To describe our pharmacovigilance program and to analyze the reported adverse drug  reactions. METHOD: Observational longitudinal study conducted from 2008 to 2016. The Pharmacy Department  leads the pharmacovigilance program and performs prospective, retrospective, intensive, and  spontaneous reporting of inpatients and outpatients (emergencies, day hospital, external consultations, and nursing homes). Each adverse drug reaction is incorporated in the  electronic health record of the patient along with an alert. RESULTS: A total of 2,631 adverse drug reactions were reported in 2,436 patients. Of these patients,  52% were men with a mean age of 63.3 [0-98] years. A total of 92.8% drug events were reported by the pharmacists and 7.2% by doctors, nurses, and technicians. A total of 63.7% were reported in  inpatients, 19.2% in emergencies, 10.6% in external consultations, 6.2% in the day hospital, and  0.3% in diagnostic radiology. There was an increase in adverse drug reactions detected by  prospective and intensive pharmacovigilance. Principal therapeutic groups involved in adverse drug  events were antineoplastic agents (21.3%), antibacterials (12.3%), antithrombotics (7.7%),  analgesics (6.7%), corticosteroids (5.2%), psycholeptics (5.2%), diuretics (4.9%),  antivirals (4.9%),  antiinflammatories and antirheumatics (4.2%), and immunosupressants (3.3%). Adverse  drug reactions mainly affected the skin and appendages (19.7%) and gastrointestinal tract (19.1%).  Adverse drug reactions were mild (38.7%), severe (30.8%), and moderate (30.5%). In total, 60.9%  of patients recovered from drug events and 31.7% were in recovery. The most frequent response was reatment interruption in 65% of cases and the patients received additional specific treatment in 56%  of cases. CONCLUSIONS: The incorporation of the pharmacovigilance program within the daily routine of the  hospital pharmacist provides added value to the safety and pharmacotherapy of the patient.

Objetivo: Describir un programa de farmacovigilancia llevado a cabo por un servicio de farmacia y  analizar las sospechas de reacciones adversas a medicamentos recogidas.Método: Estudio observacional, longitudinal, de nueve años de duración (2008-2016). El programa  de farmacovigilancia está liderado por el servicio de farmacia, que realiza farmacovigilancia  prospectiva, retrospectiva, intensiva y voluntaria en el paciente hospitalizado y ambulatorio (urgencias, hospital de día, consultas externas y centros sociosanitarios). Las reacciones  adversas se incorporan en la historia clínica electrónica del paciente y se añade una alerta que indica  su presencia.Resultados: Se recogieron 2.631 reacciones adversas a medicamentos en 2.436 pacientes (52%  varones) con una media [rango] de edad de 63,3 [0-98] años. El 92,8% de las reacciones fueron  notificadas por el farmacéutico y el 7,2% por médicos, enfermería y técnicos. El 63,7% se notificaron  en hospitalización, el 19,2% en urgencias, el 10,6% en consultas externas, el 6,2% en hospital de día  y el 0,3% en radiología. Se observó un incremento de notificación por farmacovigilancia  prospectiva e intensiva. Los grupos terapéuticos mayoritariamente implicados fueron: antineoplásicos  (21,3%), antibacterianos (12,3%), antitrombóticos (7,7%), analgésicos (6,7%), corticosteroides  (5,2%), psicolépticos (5,2%), diuréticos (4,9%), antivirales (4,9%), antiinflamatorios y  antirreumáticos (4,2%) e inmunosupresores (3,3%). Las reacciones adversas detectadas afectaron mayoritariamente a la piel y anejos (19,7%) y al tracto gastrointestinal (19,1%). Respecto a su  gravedad, el 38,7% fueron leves, el 30,8% graves y el 30,5% moderadas. El 60,9% de los pacientes  se recuperaron de las reacciones adversas y el 31,7% se encontraban en proceso de recuperación. Se  interrumpió el tratamiento en el 65% de los casos y el 56% de los pacientes recibieron  tratamiento específico.Conclusiones: La incorporación del programa de farmacovigilancia en la rutina diaria del  farmacéutico de hospital aporta un valor añadido a la seguridad de la farmacoterapia del paciente.

Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Cinacalcet use is controversial in non-dialysis patients. METHODS: This retrospective observational study recruited patients receiving cinacalcet (off-label use) in 2010 and 2011. Patients were followed for three years from the beginning of treatment using an intention-to-treat approach. RESULTS: Forty-one patients were studied: 14 CKD stage 3 (34.1%), 21 CKD stage 4 (51.2%), and 6 CKD stage 5 (14.6%). Median baseline parathyroid hormone (PTH) was 396 (101-1,300) pg/mL. Upon cinacalcet treatment (22 ± 12 months), PTH levels decreased by ≥ 30% in 73.2% of patients (P < 0.001; 95% confidence interval [CI], 59-87%), with a mean time for response of 18.7 months (95% CI, 15.4-22.1). Sixteen patients were followed for 36 months and treated for 32 ± 9 months. Mean reduction in their PTH levels was 50.1% (P < 0.001; 95% CI, 33.8-66.4%) at 36 months, with 62.5% of patients (P < 0.001; 95% CI, 35.9-89.1%) presenting reductions of ≥ 30%. Serum calcium levels decreased from 9.95 ± 0.62 mg/dL to 9.21 ± 0.83 and 9.12 ± 0.78 mg/dL at 12 and 36 months, respectively (P < 0.001). Serum phosphorus levels increased from 3.59 ± 0.43 to 3.82 ± 0.84 at 12 months (P = 0.180), remaining so at 36 months (P = 0.324). At 12 and 36 months, 2 (12.5%) patients experienced hypocalcemia. Meanwhile, 1 (6.3%) and 4 (25.0%) patients reported hyperphosphatemia at 12 and 36 months, respectively. CONCLUSION: Cinacalcet remained effective for at least 36 months in non-dialysis patients with SHPT. Electrolytic disturbances were managed with concurrent use of vitamin D and its analogs or phosphate binders.

Effectiveness of Cinacalcet in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism Not Receiving Dialysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in chronic kidney disease (CKD) patients. Cinacalcet could be a therapeutic option although its use is controversial in patients not receiving dialysis. Thus, the aim of this study is to assess the effectiveness and safety of cinacalcet in patients with CKD and SHPT without renal replacement treatment (RRT) and without renal transplantation (RT). METHODS: A retrospective observational study was conducted. Patients were included if they had collected cinacalcet, under off-label use, during 2010 and 2011. Patients selected were followed from the beginning of cinacalcet therapy for one year of treatment. RESULTS: A total of 37 patients were included with CKD stage 3 (38%), 4 (51%) and 5 (11%). Baseline mean PTH value was 400.86 ± 168.60 mg/dl. At 12 months, a 67% of patients achieved at least a 30% reduction in their PTH value (p<0.001; CI 49.7-83.6), and the overall mean reduction of PTH values was 38% (p< 0.001; IC -49.1, -27.5). A 28% of the patients achieved KDOQI PTH goals (p = 0.003, CI 12%-50%). At 12 months, mean serum calcium values decreased by 6% and mean serum phosphorus values increased by 13%. A 19% of patients experienced hypocalcemia episodes while an increase of 24% in hyperphosphatemia episodes was observed. A 25% of patients finished cinacalcet before a year of treatment. Main withdrawal reasons were: gastrointestinal and other discomfort (8%), hypocalcaemia (8%), non-compliance (3%), interactions (3%) and excess of efficacy (3%). CONCLUSIONS: Cinacalcet was effective in patients with CKD and SHPT not receiving dialysis. Electrolytic imbalances could be managed with administration of vitamin D and analogues or phosphate binders.

Adhesión terapéutica a tratamiento inmunomodulador de pacientes con esclerosis múltiple / Therapy adherence to immunomodulator treatment in patients with multiple sclerosis

Introducción. El tratamiento inmunomodulador modifica el curso de la enfermedad en los pacientes con esclerosis múltiple. Es fundamental que el paciente cumpla adecuadamente con el tratamiento pautado. Objetivo. Conocer la adhesión real al tratamiento inmunomodulador de primera línea e intentar averiguar qué factores pueden influir en el adecuado cumplimiento del tratamiento. Pacientes y métodos. Es un estudio longitudinal retrospectivo observacional de los pacientes en seguimiento por el Centre d’Esclerosi Múltiple de Catalunya del Hospital Universitari Vall d’Hebron que recogieron tratamiento inmunomodulador de primera línea (interferones o acetato de glatiramero) entre el 1 de enero de 2010 y el 30 de septiembre de 2011. La adhesión se midió utilizando el índice de posesión de medicación -medication possession ratio (MPR)-: se consideraron adherentes los pacientes con MPR mayor o igual al 80%. Resultados. Estudiamos 975 pacientes. El tiempo medio de exposición a los inmunomoduladores durante el período de recogida fue de 13,4 ± 7,1 años. El 85,2% de los pacientes tuvo una adecuada adhesión al tratamiento inmunomodulador. De 975 pacientes tratados, 134 precisaron cambiar a un segundo fármaco y 12 pacientes a un tercero. El cambio de fármaco mejoró la adhesión (p = 0,001). La tasa anual de brotes fue de 0,23. Únicamente la presencia de brotes (p = 0,029) y el fármaco utilizado (p = 0,044) tuvieron influencia en la adhesión al tratamiento, de forma individual. Conclusiones. La proporción de pacientes con adecuada adhesión al tratamiento en nuestro centro es alta. La tasa de brotes y el fármaco empleado son determinantes para ello. Se requiere un seguimiento estrecho y asesoramiento individualizado para mantener un buen cumplimiento terapéutico (AU)

Introduction. Immunomodulator treatment modifies the course of the disease in patients with multiple sclerosis. The patient’s adequate adherence with the treatment regimen is absolutely essential. Aims. To determine the real adherence with first-line immunomodulator treatment and to try to find out what factors may influence adequate adherence with the treatment. Patients and methods. We conducted an observation-based, retrospective, longitudinal study of the patients being followed up by the Centre d’Esclerosi Múltiple de Catalunya at the Hospital Universitari Vall d’Hebron that were given first-line immunomodulator treatment (interferons or glatiramer acetate) between 1st January 2010 and 30th September 2011. Adherence was measured using the medication possession ratio (MPR): patients with an MPR above or equal to 80% were considered to be compliers. Results. We studied 975 patients. The mean time of exposure to immunomodulators over the collected period was 13.4 ± 7.1 years. Altogether 85.2% of patients complied with the immunomodulator treatment adequately. Of a total of 975 patients treated, 134 needed to change to a second drug and 12 patients had to go on to a third. Changing the medication improved adherence (p = 0.001). The annual rate of attacks was 0.23. Only the presence of attacks (p = 0.029) and the drug used (p = 0.044) had any influence on treatment adherence, on an individual basis. Conclusions. The percentage of patients with adequate treatment adherence in our centre is high. The rate of attacks and the drug used play a decisive role. Close monitoring and personalised counselling are required to maintain good therapeutic adherence (AU)

[Therapy adherence to immunomodulator treatment in patients with multiple sclerosis]. / Adhesion terapeutica a tratamiento inmunomodulador de pacientes con esclerosis multiple.

INTRODUCTION: Immunomodulator treatment modifies the course of the disease in patients with multiple sclerosis. The patient's adequate adherence with the treatment regimen is absolutely essential. AIMS: To determine the real adherence with first-line immunomodulator treatment and to try to find out what factors may influence adequate adherence with the treatment. PATIENTS AND METHODS: We conducted an observation-based, retrospective, longitudinal study of the patients being followed up by the Centre d'Esclerosi Multiple de Catalunya at the Hospital Universitari Vall d'Hebron that were given first-line immunomodulator treatment (interferons or glatiramer acetate) between 1st January 2010 and 30th September 2011. Adherence was measured using the medication possession ratio (MPR): patients with an MPR above or equal to 80% were considered to be compliers. RESULTS: We studied 975 patients. The mean time of exposure to immunomodulators over the collected period was 13.4 ± 7.1 years. Altogether 85.2% of patients complied with the immunomodulator treatment adequately. Of a total of 975 patients treated, 134 needed to change to a second drug and 12 patients had to go on to a third. Changing the medication improved adherence (p = 0.001). The annual rate of attacks was 0.23. Only the presence of attacks (p = 0.029) and the drug used (p = 0.044) had any influence on treatment adherence, on an individual basis. CONCLUSIONS: The percentage of patients with adequate treatment adherence in our centre is high. The rate of attacks and the drug used play a decisive role. Close monitoring and personalised counselling are required to maintain good therapeutic adherence.